Association of the RNASE9 c.1+1G>A splice site variant with decreased sperm motility in Japanese men

IF 1.2 Q4 GENETICS & HEREDITY

Gene Reports Pub Date : 2025-12-01 Epub Date: 2025-10-28 DOI:10.1016/j.genrep.2025.102366

Shinichiro Saeki , Junko Otsuki , Noritoshi Enatsu , Xingqiang Wei , Naoto Mukaida , Ryota Okamoto , Saori Yoshimura , Keisuke Okada , Koji Chiba , Shoji Kokeguchi , Toshiroh Iwasaki , Yasuhiro Fujiwara , Mikiya Nakatsuka , Tetsuo Kunieda , Masahide Shiotani

{"title":"Association of the RNASE9 c.1+1G>A splice site variant with decreased sperm motility in Japanese men","authors":"Shinichiro Saeki , Junko Otsuki , Noritoshi Enatsu , Xingqiang Wei , Naoto Mukaida , Ryota Okamoto , Saori Yoshimura , Keisuke Okada , Koji Chiba , Shoji Kokeguchi , Toshiroh Iwasaki , Yasuhiro Fujiwara , Mikiya Nakatsuka , Tetsuo Kunieda , Masahide Shiotani","doi":"10.1016/j.genrep.2025.102366","DOIUrl":null,"url":null,"abstract":"<div><div>This study aims to investigate the role of the <em>RNASE9</em> gene mutation (c.1 + 1G > A) in male infertility, specifically focusing on its impact on sperm motility in patients with asthenozoospermia. Despite known genetic causes for azoospermia, the genetic basis of asthenozoospermia remains poorly understood. Given that <em>RNASE9</em> is specifically expressed in the epididymis, where sperm maturation occurs, we hypothesized that mutations in <em>RNASE9</em> might influence post-testicular sperm maturation. Whole-exome sequencing (WES) was performed on 20 Japanese patients with abnormal semen parameters to identify high-impact genetic variants. Variants were filtered based on allele frequencies in the 1000 Genomes Phase 3 East Asian (EAS) population and the Japanese 38KJPN database. <em>RNASE9</em> was selected for further analysis, and the presence of the c.1 + 1G > A variant was confirmed in a cohort of 71 patients via Sanger sequencing. Sperm motility and other semen parameters were evaluated, and allele frequencies in asthenozoospermic, azoospermic, and normospermic groups were compared. The allele frequency of the <em>RNASE9</em> (c.1 + 1G > A) variant was significantly higher in asthenozoospermic patients than in individuals with normal semen parameters (<em>p</em> = 0.022), while no significant difference was found in azoospermic patients. This suggests that the <em>RNASE9</em> variant primarily affects sperm motility rather than sperm production. The <em>RNASE9</em> (c.1 + 1G > A) mutation may contribute to reduced sperm motility in humans, likely impacting post-testicular sperm maturation. The findings provide new insights into the genetic factors affecting sperm motility, particularly in asthenozoospermia.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102366"},"PeriodicalIF":1.2000,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gene Reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2452014425002390","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/10/28 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}

引用次数: 0

Abstract

This study aims to investigate the role of the RNASE9 gene mutation (c.1 + 1G > A) in male infertility, specifically focusing on its impact on sperm motility in patients with asthenozoospermia. Despite known genetic causes for azoospermia, the genetic basis of asthenozoospermia remains poorly understood. Given that RNASE9 is specifically expressed in the epididymis, where sperm maturation occurs, we hypothesized that mutations in RNASE9 might influence post-testicular sperm maturation. Whole-exome sequencing (WES) was performed on 20 Japanese patients with abnormal semen parameters to identify high-impact genetic variants. Variants were filtered based on allele frequencies in the 1000 Genomes Phase 3 East Asian (EAS) population and the Japanese 38KJPN database. RNASE9 was selected for further analysis, and the presence of the c.1 + 1G > A variant was confirmed in a cohort of 71 patients via Sanger sequencing. Sperm motility and other semen parameters were evaluated, and allele frequencies in asthenozoospermic, azoospermic, and normospermic groups were compared. The allele frequency of the RNASE9 (c.1 + 1G > A) variant was significantly higher in asthenozoospermic patients than in individuals with normal semen parameters (p = 0.022), while no significant difference was found in azoospermic patients. This suggests that the RNASE9 variant primarily affects sperm motility rather than sperm production. The RNASE9 (c.1 + 1G > A) mutation may contribute to reduced sperm motility in humans, likely impacting post-testicular sperm maturation. The findings provide new insights into the genetic factors affecting sperm motility, particularly in asthenozoospermia.

查看原文本刊更多论文

RNASE9 c.1+1G>A剪接位点变异与日本男性精子活力下降的关系

本研究旨在探讨RNASE9基因突变（c.1 + 1G >； A）在男性不育中的作用，特别关注其对弱精子症患者精子活力的影响。尽管已知无精子症的遗传原因，但对无精子症的遗传基础仍然知之甚少。鉴于RNASE9在精子成熟发生的附睾中特异性表达，我们假设RNASE9的突变可能影响睾丸后精子成熟。对20例精液参数异常的日本患者进行了全外显子组测序（WES），以确定高影响遗传变异。根据1000个基因组3期东亚（EAS）人群和日本38KJPN数据库的等位基因频率筛选变异。选择RNASE9进行进一步分析，通过Sanger测序在71例患者中证实存在c.1 + 1G >； A变体。评估精子活力和其他精液参数，并比较弱精子组、无精子组和正常精子组的等位基因频率。RNASE9 （c.1 + 1G >； A）变异的等位基因频率在无精子症患者中显著高于精液参数正常的个体（p = 0.022），而在无精子症患者中无显著差异。这表明RNASE9变异主要影响精子活力而不是精子产量。RNASE9 （c.1 + 1G >； A）突变可能导致人类精子活力降低，可能影响睾丸后精子成熟。这一发现为研究影响精子活力的遗传因素提供了新的见解，特别是在弱精子症中。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.